We are studying the mechaniam by which insulin stimulates glucose transport in isolated fat cells. We have already shown that inhibition of intracellular energy metabolism such as 2-deoxyglucose, cyanide, azide or dinitrophenol partially or completely blocks the ability of the fat cell to respond to insulin by accelerated glucose transport. This is true whether the transport is measured in isolated vesicles of plasma membrane using glucose, or in the intact cell using 3-0-methyl glucose. Generally basal rates of glucose transport are not affected. We have shown that dibutyryl cyclic AMP depresses both basal as well as insulin-stimulated glucose transport. We plan to study in detail the effects of dibutyryl cyclic AMP on the kinetic parameters of 3-0-methyl glucose transport to determine if Vmax of Km is primarily affected. We then plan to study the effect of energy inhibitors on the binding of (I125) insulin to specific "receptors" on the surface of the adipose cell. Finally, we will attempt to regenerate an insulin-responsive system using isolated membrane fractions, in order to determine the nature and role of high energy intermediates in the cellular response to insulin. BIBLIOGRAPHIC REFERENCES: Chandramouli, V. and J.R. Carter, Jr. Cell Membrane Changes in Chronically Diabetic Rats, Diabetes 24:257-262, 1975.